The immune system is a major mechanism of defense against invading pathogens and disease. This important system is regulated by a series of cells and factors which can either augment or inhibit immune responsiveness. This proposal is primarily concerned with the mechanism involved in the down regulation of both cellular and humoral immunity. Over the past several years we demonstrated that at least 3 distinct T lymphocytes and a macrophage population are involved in the process of immune suppression. We plan to fully characterize the mechanisms responsible for immune suppression in a model system involving mice. Studies are to be conducted both in vivo and in vitro to permit generalization of the results. We aim to determine 1) how these suppressor T lymphocytes are induced, 2) how they acquire their specificity, 3) what controls suppressor cell activation, 4)\what molecules convey the regulatory signals, 5) what controls cellular interactions and 6) how suppressor cells and factors interact with their ultimate targets. To answer these questions we will rely on populations of cloned T cells and macrophages especially cloned hybridoma cells with proven biological activity. Over the past few years we have successfully prepared and characterized these hybridomas. Using immunological, genetic, and biochemical techniques we will study these problems at the molecular level. The results may impact broad areas of medicine, since imbalances in immune regulation have been implicated in numerous diseases including cancer.